Bone marrow-derived mesenchymal stem cells reduce brain amyloid-β deposition and accelerate the activation of microglia in an acutely induced Alzheimer's disease mouse model
Bone marrow-derived mesenchymal stem cells reduce brain amyloid-β deposition and accelerate the activation of microglia in an acutely induced Alzheimer's disease mouse model
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DOI：
10.1016/j.neulet.2008.11.059
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发表时间：
2009-01-30
影响因子：
2.5
通讯作者：
Bae, Jae-sung
中科院分区：
文献类型：
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作者：
Lee, Jong Kil;Jin, Hee Kyung;Bae, Jae-sung
最近，骨髓间充质干细胞(BM-MSCs)在中枢神经系统(CNS)的各种病理条件下的治疗潜力得到了探索。然而，骨髓间充质干细胞在急性诱导的阿尔茨海默病(AD)中的应用尚未见报道。在此，对骨髓间充质干细胞作为AD治疗剂的可行性进行了试验。为了评估这种可能性，采用了向C57BL/6小鼠海马齿状回(DG)注射淀粉样β蛋白(Aβ)诱导的急性AD模型。将骨髓间充质干细胞移植到诱导性AD模型的大脑中，与假移植动物相比，降低了它们的Aβ水平。Aβ沉积减少伴随着小胶质细胞的激活。此外，激活的小胶质细胞位于Aβ沉淀物附近，其形态由分枝状变为阿米巴样，这是小胶质细胞吞噬的标志。本研究提供了BM-MSCs可通过激活小胶质细胞促进AD脑内Aβ降低的证据，提示BM-MSCs有可能成为治疗AD的药物。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利
The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has recently been explored in various pathological conditions of the central nervous system (CNS). However, the application of BM-MSCs in acutely induced Alzheimer's disease (AD) has not yet been reported. Herein the feasibility of using the BM-MSCs, as a therapeutic agent for AD has been tested. To assess this possibility, an acutely induced AD model induced by injecting amyloid-beta (A beta) into the dentate gyrus (DG) of hippocampus of C57BL/6 mice was used. Intracerebral transplantation of BM-MSCs into the brain of an induced AD model reduced their A beta levels when compared to sham-transplanted animals. The diminution of A beta deposits was accompanied by the activation of microglia. In addition, the activated microglia was located near the A beta deposits, and their morphology was changed from ramified to ameboid as a sign of microglial phagocytosis. This study provides evidence that BM-MSCs can promote the reduction of A beta through the microglial activation in this acutely induced AD brain, suggesting a potential therapeutic agent against AD. (C) 2008 Elsevier Ireland Ltd. All rights reserved